中国全科医学 ›› 2023, Vol. 26 ›› Issue (17): 2070-2077.DOI: 10.12114/j.issn.1007-9572.2023.0048

• 论著 • 上一篇    下一篇

基于人工智能算法的脑卒中溶栓药物精准治疗:真实世界研究

沈惠文1, 林永忠2, 陈淑良3, 张立红4, 马春野2, 马得原1, 张策1,*()   

  1. 1.116027 辽宁省大连市,大连医科大学附属第二医院发展规划与质量管理部 2.116027 辽宁省大连市,大连医科大学附属第二医院神经内科 3.116027 辽宁省大连市,大连医科大学附属第二医院护理部 4.116027 辽宁省大连市中心医院介入及神经重症科
  • 收稿日期:2023-01-07 修回日期:2023-03-01 出版日期:2023-06-15 发布日期:2023-03-09
  • 通讯作者: 张策

  • 作者贡献:沈惠文负责数据收集和整理,统计学处理,并撰写论文初稿;林永忠提出主要研究指标;陈淑良负责纳排标准的制定;张立红负责究对象的选取;马春野负责论文修订;马得原负责数据收集和整理;张策负责研究的质量控制及审校,并对研究负责;所有作者确认了论文的最终稿。
  • 基金资助:
    大连医科大学附属第二医院"1+X"计划临床研究孵化项目(2022LCYJYB05)

Precise Thrombolytic Treatment for Stroke Using AI-based Algorithms: a Real-world Study

SHEN Huiwen1, LIN Yongzhong2, CHEN Shuliang3, ZHANG Lihong4, MA Chunye2, MA Deyuan1, ZHANG Ce1,*()   

  1. 1. Development Planning and Quality Management Department, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China 2. Department of Neurology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China 3. Nursing Department, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China 4. Department of Intervention and Neurocritical Care, Dalian Municipal Central Hospital, Dalian 116027, China
  • Received:2023-01-07 Revised:2023-03-01 Published:2023-06-15 Online:2023-03-09
  • Contact: ZHANG Ce

摘要: 背景 缺血性脑卒中(IS)起病急,治疗时间窗窄,治疗效果的影响因素复杂,患者自身情况各异,因此治疗方式、给药种类、给药剂量、给药方式均会影响患者的溶栓效果。既往研究常利用统计方法分析溶栓效果的影响因素,人工智能算法在该方面的临床应用尚少见。目的 基于真实世界的数据,建立IS患者从一般特征、药物治疗方式到恢复效果的人工智能算法模型,实现个体化溶栓药物精准治疗,为临床用药决策提供数据支持。方法 采用回顾性研究方式,从大连医科大学附属第二医院医渡云科研大数据服务器系统提取本院确诊为IS患者(n=55 621)的临床信息,时间为2001-01-01至2021-12-31。依据纳入标准共筛选出信息完整的IS患者1 855例,依据每位患者入院与出院时美国国立卫生研究院卒中量表(NIHSS)评分差值评价患者溶栓效果,并将患者分为神经功能改善组(差值≥4分,n=1 236)和对照组(差值<4分,n=619)。经3位神经内科高级职称专家背对背推荐,并结合查阅的IS诊治指南及文献,整理可能与IS发作后溶栓效果相关的影响因素,归类为患者一般特征、用药指标、检查指标、检验指标、治疗方式5类。首先进行影响因素的单因素筛选,再利用主成分分析法对影响因素做降维处理。构建Logistic回归模型、支持向量机(SVM)、C5.0决策树、分类回归树(CART)、深度神经网络(DNN)及Wide&Deep模型,进行模型对比评价,比较不同模型对IS患者溶栓效果的预测情况,确定最佳模型,进而寻找模型的最优参数。将1 855例患者的临床信息进行分割处理,随机数为7和11,随机分为训练集(1 113例)、验证集(371例)、测试集(371例),其中训练集用来构建和训练模型以发现规律,验证集用来调整模型参数,测试集用来评价最终模型的泛化能力。应用特征工程构建简化模型并评估模型准确度。从大连市中心医院的医渡云科研大数据服务器系统中提取IS患者的临床信息(共提取3 925例),利用其数据进行外部验证。结果 共纳入26个患者特征(即溶栓效果影响因素)进行模型构建。经主成分分析降维成2个主成分,累积方差贡献率为93.1%。比较Logistic回归模型、SVM、C5.0决策树、CART、DNN及Wide&Deep模型预测溶栓效果的价值,发现Wide&Deep模型的预测性能最佳,准确度为0.815,F指数为0.871。训练集受试者工作特征(ROC)曲线下面积为0.753,测试集ROC曲线下面积为0.793。确定Wide&Deep模型的隐含层层数为7层,每层神经元个数为15个,以Sigmoid作为激活函数,模型参数最优。IS患者溶栓治疗后神经功能改善影响因素的特征工程分析结果显示,用药种类、给药方式和用药剂量的重要性排序均在前列,重要性排序由大到小分别为:是否有脑血管病史、用药种类、给药方式、单次剂量、动脉粥样硬化、溶栓时间窗、是否使用抗凝药物和活血化瘀药物等。模型自变量简化后得出,Wide&Deep模型准确度为0.819,模型自变量简化后外部验证的准确度为0.801。结论 Wide&Deep模型各项评价指标优异,影响溶栓效果的因素排序由大到小分别为:是否有脑血管病史、用药种类、给药方式、单次剂量、动脉粥样硬化、溶栓时间窗、是否使用抗凝药物和活血化瘀药物等。通过人工智能算法从影响因素和个体化给药方面可为临床医生提供及时和有效的IS患者药物溶栓治疗方案,对减轻疾病社会负担具有积极意义。

关键词: 缺血性卒中, 溶栓药物, 人工智能算法, Wide&Deep模型, 精准治疗

Abstract: Background The thrombolytic effect for ischemic stroke (IS) is affected by complex factors, such as acute onset of stroke, short therapeutic time window, various individual patient factors, treatment model, types and doses of medicines as well as mode of administration. To identify the influencing factors of thrombolytic effect, most existing studies adopt statistical methods, while rare studies use artificial intelligence (AI) -based algorithms.Objective To establish models using AI-based algorithms for IS patients based on the real-world data including general patient characteristics, medication model and recovery effects, to achieve precise individualized thrombolytic treatment and provide data support for clinical prescription decisions.Methods A retrospective design was used. The clinical information of IS patients (n=55 621) was extracted from the Yidu Cloud scientific research big data server system of the Second Affiliated Hospital of Dalian Medical University from January 1, 2001 to December 31, 2021, among whom 1 855 with complete information were enrolled according to the inclusion criteria. Thrombolysis effect was evaluated by comparing the National Institutes of Health Stroke Scale (NIHSS) score measured at admission and discharge, and those with an improvement in the NIHSS score by ≥4 points and <4 points were assigned to neurological improvement group (n=1 236) , and control group (n=619) , respectively. Factors possibly associated with post-IS thrombolytic effect (including general patient characteristics, medication indicators, examination indicators, test indicators, and treatment methods) were obtained by summarizing the factors suggested separately by three neurology experts with a senior title, and reviewing relevant guidelines and literature, then were screened using univariate analysis, and the identified ones were treated by dimensionality reduction using principal component analysis (PCA) . Models of Logistic, support vector machine (SVM) , C5.0 decision tree arithmetic, classification and regression tree (CART) , deep neural network (DNN) , and Wide&Deep, were built and compared to find the one with the best performance in predicting thrombolytic effect, then to determine its parameters. Then by use of two randomly generated two numbers, 7 and 11, the 1 855 patients were randomly assigned to three datasets, training (n=1 113, for building and practicing models to discover rules) , validation (n=371, for adjusting model parameters) , and test (n=371, for evaluating the generalization ability of the final model) . Feature engineering was used to construct a simplified model and evaluate its accuracy. The clinical information of IS patients (n=3 925) was extracted from the Yidu Cloud scientific research big data server system of Dalian Central Hospital for external verification of the model.

Results

Twenty-six patients characteristics associated with thrombolytic effect were included for establishing models. The dimensionalities were reduced to two principal components by PCA, explaining 93.1% of the total variance. Comparison analysis revealed that the Wide&Deep model had the best predictive performance with an accuracy of 0.815, and an F-index of 0.871. Furthermore, the values of the area under the receiver operating characteristic (AUC) curve of the Wide&Deep model in predicting the thrombolytic effect in patients in the training set and test set were 0.753 and 0.793, respectively. The number of hidden layers and neurons in each layer of the model was 7 and 15, respectively. Using sigmoid as the activation function showed that the model parameters were optimal. The feature-engineering analysis of factors influencing the improvement of neurological function showed that the importance of medication type, administration mode and dosage ranked high, and the importance ranking in a descending order was: cerebrovascular disease history, type of medication, mode of administration, single dose, atherosclerosis, therapeutic time window of thrombolytic therapy, prevalence of use of anticoagulant drugs and drugs for promoting blood circulation and removing blood stasis. After simplifying the independent variables of the model, the accuracy of the Wide&Deep model was 0.819, and its accuracy was 0.801 suggested by the external verification after model simplification, indicating good predictive performance and generalizability.Conclusion The Wide&Deep model has proven to have excellent evaluation indicators. The importance of influencing factors of thrombolytic effect in a descending order is: cerebrovascular disease history, type of medication, administration mode, single dose, atherosclerosis, therapeutic time window of thrombolytic therapy, prevalence of use of anticoagulants and blood-activating and stasis-removing drugs. It provides clinicians with timely and effective thrombolysis treatment support involving thrombolysis related factors and individualized administration using AI-based algorithms.

Key words: Ischemic stroke, Thrombolytic drugs, Artificial intelligence algorithm, Wide&Deep model, Precision treatment